Maja Ivković

Low bone mineral density and high bone metabolism turnover in premenopausal women with unipolar depression.

INTRODUCTION AND HYPOTHESIS The majority of studies reporting decreased bone mineral density (BMD) in patients with unipolar depression neglected sex and age differences and menopause as the most important risk factor for osteoporosis. We presumed that physically healthy premenopausal women with unipolar depression have decreased BMD and altered bone cell metabolism. METHODS BMD at lumbar spine and femoral neck by dual X-ray absorptiometry, bone alkaline phosphatase sera activity, 5b-tartarate resistant acid phosphatase sera activity and urine N-terminal telopeptide were measured in 73 premenopausal women with unipolar depression and compared with 47 healthy, age- and osteoporosis risk factors-matched premenopausal women. The duration and severity of depression, hormonal status (cortisol, prolactin, parathormone, oestradiol), antidepressive treatment, and physical activity through whole and modified QUALEFFO-41 questionnaire were evaluated. The results were statistically elaborated by the chi-square test, Students t-test for independent samples, one-way analysis of variance - ANOVA, one-sample Kolmogorov-Smirnov test. Correlations were assessed by means of Pearsons coefficient. RESULTS Patients with unipolar depression had significantly lower BMD, the decrease of which correlated only with the duration of depression. High bone metabolism turnover was found with a predomination of osteoresorption which, but not osteosynthesis, correlated with the severity of depression, estimated through Hamilton depression scores. Despite higher but not significant levels of cortisol in women with unipolar depression, the BMD decrease and high bone turnover seem not to be the consequence of hormonal changes or medical treatment. The significant correlations between physical activity and osteoresorption markers were found indicating possible underlying mechanism. CONCLUSIONS Premenopausal women with unipolar depression have significantly lower BMD because of stimulated bone cell metabolism with predomination of osteoresorption process, mostly due to decreased physical activity in depression. These women should be investigated for osteoporosis and the multidisciplinary team approach is advocated.

Melancholic and atypical major depression--connection between cytokines, psychopathology and treatment.

BACKGROUND AND PURPOSE Growing scientific evidence indicates that there is a correlation between depression and alternations in the immune system. The main aim of the study was to investigate serum levels of Interleukin-6 (IL-6) and Tumour Necrosis Factor-alpha (TNF-α) in melancholic and atypical depressive patients during acute exacerbations of illness, compared to healthy subjects. The secondary aim was to explore a possible association between cytokine levels and clinical characteristics, as well as total duration of prior antidepressant treatment. METHOD We measured serum levels of IL-6 and TNF-α in 47 patients suffering from major depressive disorder (MDD) (29 melancholic and 18 atypical) in exacerbation of illness, compared to 39 healthy controls, matched by sex, body mass index (BMI) and smoking habits. Serum levels of IL-6 and TNF-α were measured by enzyme-linked immunosorbent assay (ELISA). The severity of psychopathology was assessed using the Hamilton Depression Rating Scale (HDRS). RESULTS IL-6 was significantly elevated in melancholic depressive patients (MDD-M) compared to healthy controls, while no difference was found between the patients with atypical depression (MDD-A) and the healthy group. Lower TNF-α serum level was found both in melancholic and in patients with atypical depression, compared with healthy subjects. We detected a positive correlation between cytokine levels in atypical, but not in melancholic subjects. Sex, age, smoking habits and BMI were not associated to cytokine levels in neither group. Clinical parameters (duration of illness, current episode, age of onset) were related to cytokine levels in atypical depression, while the duration of lifetime exposure to antidepressant treatment correlated to IL-6 serum levels in both melancholic and atypical depression. CONCLUSION Our results suggest that the difference in pro-inflammatory cytokine levels could reflect a biological difference between melancholic and atypical depression. A positive correlation between the cytokines (TNF-α and IL-6) observed in depressive patients with atypical features, might be influenced by chronic course of illness, while IL-6 elevation could represent a state indicator for acute exacerbation, especially in melancholic patients. Total duration of antidepressant treatment could be a relevant factor influencing the immune status of patients who suffer either from melancholic or atypical depression.

Plasma homocysteine levels in young male patients in the exacerbation and remission phase of schizophrenia.

High levels of homocysteine (Hcy) were suggested to contribute to the pathogenesis of schizophrenia. Recent investigations have shown that treatment with folic acid, vitamin B-12 and pyridoxine are effective in reducing Hcy levels while concomitantly reducing the score of positive and negative symptoms in schizophrenic patients. In addition to the availability of nutrients (mainly folate, vitamins B6 and B12), plasma Hcy concentrations are dependent on complex metabolic regulation that could be disrupted in schizophrenia. This study was designed to test the influence of disease activity on plasma Hcy levels. Plasma Hcy concentrations were measured in male chronic schizophrenic patients with a predominantly positive (SCH (+)) or predominantly negative (SCH (-)) syndrome in schizophrenia immediately upon admission to the hospital (exacerbation phase) and one month later (remission phase). During this period patients received antipsychotic medications without vitamin therapy. The effects of age, duration of illness, folate and B12 concentrations, as well as smoking and coffee consumption habits on the observed changes were evaluated. Age- and sex-matched subjects were included in the control group. In the control group plasma Hcy concentration was 8.75+/-1.84 micromol/L. In the exacerbation phase plasma Hcy concentrations were significantly increased both in SCH (+) (14.91+/-6.19 micromol/L) and SCH (-) groups (12.8+/-3.27 micromol/L). There was no difference in plasma Hcy concentrations between SCH (+) and SCH (-) patients. Serum folate and B12 concentrations were not significantly different in any of the investigated groups of subjects. The plasma Hcy concentrations could not be correlated with age, duration of illness, the score of positive symptoms or the concentration of folate and vitamin B12. A positive correlation was found between plasma Hcy level and score of negative symptoms in both groups of patients. No correlation was found between smoking or coffee consumption habits and plasma Hcy concentrations. All patients exhibited decreased plasma Hcy levels in the remission phase of the illness, with a mean decrease of 2.68+/-1.57 micromol/L. Folate and B12 levels did not differ in the exacerbation and remission phases of the illness. The significant decrease of plasma Hcy levels, without changes in folate and vitamin B12 concentrations in the remission phase of schizophrenia, could indicate an influence of a pathogenetic process involved in schizophrenia on Hcy metabolism.

Joint effect of ADARB1 gene, HTR2C gene and stressful life events on suicide attempt risk in patients with major psychiatric disorders

Abstract Objectives. Adenosine to inosine RNA editing, serotonin 2C receptor (HTR2C), and stressful life events (SLEs) have all been implicated in suicidal behaviour. We examined the main and moderating effects of RNA editing (ADAR, ADARB1) and HTR2C genes, childhood trauma (CT), recent SLEs and psychiatric disorders as contributors to suicide attempt (SA) vulnerability. Methods. Study included 165 suicide attempters and 188 suicide non-attempters, all diagnosed with one of major psychiatric disorders. CT and recent SLEs were assessed using Early Trauma Inventory–Self Report and List of Threatening Experiences Questionnaire, respectively. Selected ADAR and ADARB1 tag-variants, and HTR2C rs6318 were pre-screened for association with SA, while generalized linear models and backward selection were applied to identify individual and interacting SA risk factors. Results. ADARB1 rs9983925 and rs4819035 and HTR2C rs6318 were associated with SA. The best minimal model found emotional abuse, recent SLEs, rs9983925 and rs6318 as independent SA risk factors, and general traumas as a factor moderating the effect of psychiatric disorders and emotional abuse. Conclusions. SA vulnerability in psychiatric patients is related to the joint effect of ADARB1 and HTR2C variants, the existing mood disorder and the cumulative exposures to a various childhood and recent stressful experiences.

Neutrophil-to-lymphocyte ratio predicting suicide risk in euthymic patients with bipolar disorder: Moderatory effect of family history

BACKGROUND Neutrophil-to-lymphocyte ratio (NLR) has been independently related to bipolar disorder (BD) and factors associated with suicidal risk. The aim of our study was to explore the relationship between NLR and suicide risk in euthymic BD patients. We also sought to propose a model of interaction between NLR and stress-diathesis factors, leading to suicidal risk in BD. METHODS The study group consisted of 83 patients diagnosed with BD (36 suicide attempters; 47 suicide non-attempters), compared to the healthy control group (n=73) and matched according to age, gender, and body mass index (BMI). NLR was measured according to the complete blood count. Mood symptoms have been assessed by Young Mania Rating Scale and Montgomery-Asberg Depression Rating Scale. Early trauma and acute stress were evaluated by Early Trauma Inventory Self Report-Short Form and List of Threatening Experiences Questionnaire, respectively. Suicide risk has been assessed by Suicide Behaviors Questionnaire-Revised (SBQ-R). RESULTS Significant correlation was found between NLR and SBQ-R score. The main effects of suicide attempts on NLR, after covarying for confounders, were observed, indicating increased NLR in BD suicide attempters compared to healthy controls. We found significant moderatory effects of family history on NLR relationship to suicidal risk, with NLR being significant positive predictor of suicidal risk only in the patients with positive family history of suicide attempts. CONCLUSIONS The results suggest an enhancing effect of positive family history of suicide attempts on predictive effect of NLR on suicide risk. Our data support the idea that immune markers can predict suicide attempt risk in BD, but only in the subpopulation of BD patients with family history of suicide attempts. This could lead to prevention in suicide behavior in the patient population at particular risk of suicide.

Schizophrenia and polymorphic CAG repeats array of calcium-activated potassium channel (KCNN3) gene in Serbian population.

KCNN3 might be a candidate gene for schizophrenia. The KCNN3 cDNA sequence contains two stretches of CAG trinucleotide repeats encoding two separate polyglutamine segments near the N-terminus of this channel protein. The second CAG repeat is highly polymorphic in the Caucasian population from both Europe and United States. The authors carried out a study to compare the allelic frequency distribution of the CAG repeat in KCNN3 gene in 55 Serbian schizophrenic patients and 46 controls. The data indicate a significant association between longer CAG repeats in second polymorphic KCNN3 region and schizophrenia in the Serbian population.

Dementia paralytica (neurosyphilis): A clinical case study

Summary This study reminds clinicians that syphilis presents in many guises. Wars, migration and sexual promiscuity prepare the ground for its return as an important cause of neurological and psychiatric syndromes. Our patients diagnosis was not suspected at earlier admission. Stage III spirochaetosis was improved by high dose penicillin.

Role of sICAM-1 and sVCAM-1 as biomarkers in early and late stages of schizophrenia.

Schizophrenia (SZ) is a neuroprogressive disorder presenting with biochemical, functional, and structural changes, which differ from early to late stages of the illness. We explored the differences in serum levels of soluble intercellular cell adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) between early and late stages of SZ, in regard to clinical characteristics and treatment application. Serum levels of sICAM-1 and sVCAM-1 were measured in 80 patients with SZ (40 early stage; 40 late stage), and compared with 80 healthy controls, matched by age, gender, body mass index, and smoking habits with each SZ group. Serum levels of sICAM-1 and sVCAM-1 were measured using ELISA. The severity of psychopathology was assessed using the Clinical Global Impression Scale and five-factor Positive and Negative Symptoms in Schizophrenia Scale. After adjustment for confounders, we noticed normal levels of sICAM-1 in the early stage, and elevated levels of sICAM-1 in the late stage of SZ. sVCAM-1 levels were decreased in both stages of SZ. Higher sICAM-1 levels have been related to more pronounced cognitive deficit and excitement symptoms in the early stage of SZ and to favorable characteristics of treatment application in both stages. SZ is associated with changes in the levels of adhesion molecules that vary from early to late stages of the illness. This implies that the concept of biochemical staging is applicable in SZ, at least for markers of cellular adhesion.

Schizophrenia and Apolipoprotein E Gene Polymorphism in Serbian Population

ABSTRACT Apolipoprotein E (APOE) gene variants are associated with alterations in brain function and increased risk of Alzheimers disease (AD) and conflicting results have been reported in schizophrenia. Our results showed no significant differences in APOE allele or genotype frequencies between the Serbian schizophrenic patients and control individuals. However, we observed a possible association between particular subtypes of schizophrenia and APOE ε3/ε3 genotype (p = .01221) and ε4 allele showed a tendency toward positive association with responding to typical neuroleptics. APOE genotypes have no major influence on risk of schizophrenia, treatment and response to conventional antipsychotics, and age of onset in schizophrenia.

Tryptophan Hydroxylase 1 Variant rs1800532 is Associated with Suicide Attempt in Serbian Psychiatric Patients but does not Moderate the Effect of Recent Stressful Life Events

Tryptophan hydroxylase 1 (TPH1) gene, coding for serotonin synthesizing enzyme, and recent stressful life events (SLEs) have been commonly associated with suicidal behavior. TPH1 has been also hypothesized to be involved in stress-response mechanisms. The aim of this study was to assess TPH1 variant rs1800532 and its possible interaction with recent SLEs as risk factors for suicide attempt (SA) in Serbian psychiatric patients, including 165 suicide attempters and 188 suicide nonattempters. rs1800532 and recent SLEs were independently associated with SA, while rs1800532 did not moderate the effect of recent SLEs on SA vulnerability among Serbian psychiatric patients.